Spectrin-like repeats 11-15 of human dystrophin show adaptations to a lipidic environment

Dystrophin is essential to skeletal muscle function and confers resistance to the sarcolemma by interacting with cytoskeleton and membrane. In the present work, we characterized the behavior of dystrophin 11-15 (DYS R11-15), five spectrin-like repeats from the central domain of human dystrophin, with lipids. DYS R11-15 displays an amphiphilic character at the liquid/air interface while maintaining its secondary α-helical structure. The interaction of DYS R11-15 with small unilamellar vesicles (SUVs) depends on the lipid nature, which is not the case with large unilamellar vesicles (LUVs). In addition, switching from anionic SUVs to anionic LUVs suggests the lipid packing as a crucial factor for the interaction of protein and lipid. The monolayer model and the modulation of surface pressure aim to mimic the muscle at work (i.e. dynamic changes of muscle membrane during contraction and relaxation) (high and low surface pressure). Strikingly, the lateral pressure modifies the protein organization. Increasing the lateral pressure leads the proteins to be organized in a regular network. Nevertheless, a different protein conformation after its binding to monolayer is revealed by trypsin proteolysis. Label-free quantification by nano-LC/MS/MS allowed identification of the helices in repeats 12 and 13 involved in the interaction with anionic SUVs. These results, combined with our previous studies, indicate that DYS R11-15 constitutes the only part of dystrophin that interacts with anionic as well as zwitterionic lipids and adapts its interaction and organization depending on lipid packing and lipid nature. We provide strong experimental evidence for a physiological role of the central domain of dystrophin in sarcolemma scaffolding through modulation of lipid-protein interactions.     

Breeding habitat selection behaviors in heterogeneous environments: implications for modeling reintroduction

Animal movement and habitat selection behavior are important considerations in ecology, and remain a major issue for successful animal reintroductions. However, simple rules are often used to model movement or focus only on intrinsic environmental cues, neglecting recent insights in behavioral ecology on habitat selection processes. In particular, social information has been proposed as a widespread source of information for habitat evaluation.
We investigated the role of explicit breeding habitat selection strategies on the establishment pattern of reintroduced populations and their persistence. We considered local movement at the scale of a single population. We constructed a spatially-implicit demographic model that considered five breeding habitat selection rules: 1) random, 2) intrinsic habitat quality, 3) avoidance of conspecifics, 4) presence of conspecifics and 5) reproductive success of conspecifics. The impact of breeding habitat selection was examined for different release methods under various levels of environmental heterogeneity levels, for both long and short-lived monogamous species.
When heterogeneity between intrinsic habitat patch qualities is high, the persistence of reintroduced populations strongly depends on habitat selection strategies. Strategies based on intrinsic quality and conspecific reproductive success lead to a lower reintroduction failure risk than random, conspecific presence or avoidance-based strategies. Conspecific presence or avoidance-based strategies may aggregate individuals in suboptimal habitats. The release of adults seems to be more efficient independent of habitat selection strategy.
We emphasize the crucial role of oriented habitat selection behavior and non ideal habitat selection in movement modeling, particularly for reintroduction.     

Integrating population genetics to define conservation units from the core to the edge of Rhinolophus ferrumequinum western range

The greater horseshoe bat (Rhinolophus ferrumequinum) is among the most widespread bat species in Europe but it has experienced severe declines, especially in Northern Europe. This species is listed Near Threatened in the European IUCN Red List of Threatened Animals, and it is considered to be highly sensitive to human activities and particularly to habitat fragmentation. Therefore, understanding the population boundaries and demographic history of populations of this species is of primary importance to assess relevant conservation strategies. In this study, we used 17 microsatellite markers to assess the genetic diversity, the genetic structure, and the demographic history of R. ferrumequinum colonies in the western part of its distribution. We identified one large population showing high levels of genetic diversity and large population size. Lower estimates were found in England and northern France. Analyses of clustering and isolation by distance suggested that the Channel and the Mediterranean seas could impede R. ferrumequinum gene flow. These results provide important information to improve the delineation of R. ferrumequinum management units. We suggest that a large management unit corresponding to the population ranging from Spanish Basque Country to northern France must be considered. Particular attention should be given to mating territories as they seem to play a key role in maintaining high levels of genetic mixing between colonies. Smaller management units corresponding to English and northern France colonies must also be implemented. These insular or peripheral colonies could be at higher risk of extinction in the near future.     

Evolution of equal division among unequal partners

One of the hallmarks of human fairness is its insensitivity to power: although strong individuals are often in a position to coerce weak individuals, fairness requires them to share the benefits of cooperation equally. The existence of such egalitarianism is poorly explained by current evolutionary models. We present a model based on cooperation and partner choice that can account for the emergence of a psychological disposition toward fairness, whatever the balance of power between the cooperative partners. We model the evolution of the division of a benefit in an interaction similar to an ultimatum game, in a population made up of individuals of variable strength. The model shows that strong individuals will not receive any advantage from their strength, instead having to share the benefits of cooperation equally with weak individuals at the evolutionary equilibrium, a result that is robust to variations in population size and the proportion of weak individuals. We discuss how this model suggests an explanation for why egalitarian behaviors toward everyone, including the weak, should be more likely to evolve in humans than in any other species.     

Unconventional surface plasmon resonance signals reveal quantitative inhibition of transcriptional repressor EthR by synthetic ligands

EthR is a mycobacterial repressor that limits the bioactivation of ethionamide, a commonly used anti-tuberculosis second-line drug. Several efforts have been deployed to identify EthR inhibitors abolishing the DNA-binding activity of the repressor. This led to the demonstration that stimulating the bioactivation of Eth through EthR inhibition could be an alternative way to fight Mycobacterium tuberculosis. We propose a new surface plasmon resonance (SPR) methodology to study the affinity between inhibitors and EthR. Interestingly, the binding between inhibitors and immobilized EthR produced a dose-dependent negative SPR signal. We demonstrate that this signal reveals the affinity of small molecules for the repressor. The affinity constants (K_D) correlate with their capacity to inhibit the binding of EthR to DNA. We hypothesize that conformational changes in EthR during ligand interaction could be responsible for this SPR signal. Practically, this unconventional result opens perspectives onto the development of an SPR assay that would at the same time reveal structural changes in the target upon binding with an inhibitor and the binding constant of this interaction.     

Sex‐chromosome differentiation parallels postglacial range expansion in European tree frogs (Hyla arborea)

Occasional XY recombination is a proposed explanation for the sex‐chromosome homomorphy in European tree frogs. Numerous laboratory crosses, however, failed to detect any event of male recombination, and a detailed survey of NW‐European Hyla arborea populations identified male‐specific alleles at sex‐linked loci, pointing to the absence of XY recombination in their recent history. Here, we address this paradox in a phylogeographic framework by genotyping sex‐linked microsatellite markers in populations and sibships from the entire species range. Contrasting with postglacial populations of NW Europe, which display complete absence of XY recombination and strong sex‐chromosome differentiation, refugial populations of the southern Balkans and Adriatic coast show limited XY recombination and large overlaps in allele frequencies. Geographically and historically intermediate populations of the Pannonian Basin show intermediate patterns of XY differentiation. Even in populations where X and Y occasionally recombine, the genetic diversity of Y haplotypes is reduced below the levels expected from the fourfold drop in copy numbers. This study is the first in which X and Y haplotypes could be phased over the distribution range in a species with homomorphic sex chromosomes; it shows that XY‐recombination patterns may differ strikingly between conspecific populations, and that recombination arrest may evolve rapidly (<5000 generations).     

Matrikines from basement membrane collagens: A new anti-cancer strategy

Background

Tumor microenvironment is a complex system composed of a largely altered extracellular matrix with different cell types that determine angiogenic responses and tumor progression. Upon the influence of hypoxia, tumor cells secrete cytokines that activate stromal cells to produce proteases and angiogenic factors. In addition to stromal ECM breakdown, proteases exert various pro- or anti-tumorigenic functions and participate in the release of various ECM fragments, named matrikines or matricryptins, capable to act as endogenous angiogenesis inhibitors and to limit tumor progression.

Scope of review

We will focus on the matrikines derived from the NC1 domains of the different constitutive chains of basement membrane-associated collagens and mainly collagen IV.

Major conclusions

The putative targets of the matrikine control are the proliferation and invasive properties of tumor or inflammatory cells, and the angiogenic and lymphangiogenic responses. Collagen-derived matrikines such as canstatin, tumstatin or tetrastatin for example, decrease tumor growth in various cancer models. Their anti-cancer activities comprise anti-proliferative effects on tumor or endothelial cells by induction of apoptosis or cell cycle blockade and the induction of a loss of their migratory phenotype. They were used in various preclinical therapeutic strategies: i) induction of their overexpression by cancer cells or by the host cells, ii) use of recombinant proteins or synthetic peptides or structural analogues designed from the structure of the active sequences, iii) used in combined therapies with conventional chemotherapy or radiotherapy.

General significance

Collagen-derived matrikines strongly inhibited tumor growth in many preclinical cancer models in mouse. They constitute a new family of anti-cancer agents able to limit cancer progression. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.     

Growing biodiverse carbon‐rich forests

Regrowing forests on cleared land is a key strategy to achieve both biodiversity conservation and climate change mitigation globally. Maximizing these co‐benefits, however, remains theoretically and technically challenging because of the complex relationship between carbon sequestration and biodiversity in forests, the strong influence of climate variability and landscape position on forest development, the large number of restoration strategies possible, and long time‐frames needed to declare success. Through the synthesis of three decades of knowledge on forest dynamics and plant functional traits combined with decision science, we demonstrate that we cannot always maximize carbon sequestration by simply increasing the functional trait diversity of trees planted. The relationships between plant functional diversity, carbon sequestration rates above ground and in the soil are dependent on climate and landscape positions. We show how to manage ‘identities’ and ‘complementarities’ between plant functional traits to achieve systematically maximal cobenefits in various climate and landscape contexts. We provide examples of optimal planting and thinning rules that satisfy this ecological strategy and guide the restoration of forests that are rich in both carbon and plant functional diversity. Our framework provides the first mechanistic approach for generating decision‐makingrules that can be used to manage forests for multiple objectives, and supports joined carbon credit and biodiversity conservation initiatives, such as Reducing Emissions from Deforestation and forest Degradation REDD+. The decision framework can also be linked to species distribution models and socio‐economic models to find restoration solutions that maximize simultaneously biodiversity, carbon stocks, and other ecosystem services across landscapes. Our study provides the foundation for developing and testing cost‐effective and adaptable forest management rules to achieve biodiversity, carbon sequestration, and other socio‐economic co‐benefits under global change.